復發性口腔潰瘍患者之自體抗體、貧血及補血素缺乏研究

Autoantibodies, anemia, and hematinic deficiencies in patients with recurrent aphthous stomatitis

巫仰哲(Yang-Che Wu)

指導教授 ： 江俊斌

共同指導教授 ： 陳信銘 ； 孫安迪

國立臺灣大學/醫學院/臨床牙醫學研究所/博士(2018年)

https://doi.org/10.6342/NTU201802472

摘要

背景/目的：復發性口腔潰瘍(recurrent aphthous stomatitis, RAS)是一種常見發生於非角化黏膜且疼痛之口腔潰瘍疾病，部分復發性口腔潰瘍患者會合併萎縮性舌炎(atrophic glossitis, AG)。本研究之主要目的為檢驗不同型態RAS患者血清中之胃壁細胞抗體（gastric parietal cell antibody, GPCA）、甲狀腺球蛋白抗體（thyroglobulin antibody, TGA）、甲狀腺微小體抗體（thyroid microsomal antibody, TMA）出現頻率，評估AG陽性RAS (AG+/RAS) 患者及AG陰性RAS (AG-/RAS) 患者是否有貧血及補血素缺乏之情形，評估RAS合併AG或RAS疾病本身是否為造成AG+/RAS及AG-/RAS患者貧血及補血素缺乏之重要因子。

方法：本研究之主要方法為量測355位RAS患者及355位年齡、性別相符之控制組個體之平均血色素、血清鐵、維生素B12、葉酸、GPCA、TGA及 TMA濃度。

結果：我們發現13.0%、19.4% 及 19.7%之355位RAS患者，16.7%、23.3% 及 21.7%之60位大型(major-typed) RAS患者，12.2%、18.6% 及19.3%之295位小型(minor-typed) RAS患者，18.1%、20.0% 及 21.9%之160位AG+/RAS患者，及8.7%、19.0% 及 17.9%之195位AG-/RAS患者，其血清中分別有GPCA、TGA及 TMA自體抗體出現。RAS、大型RAS、小型RAS 、AG+/RAS、AG-/RAS患者之GPCA、TGA及 TMA自體抗體出現頻率，皆比健康控制組個體為高(所有P值皆< 0.001)。65位TGA/TMA陽性RAS患者有量測血清中甲狀腺刺激素(thyroid-stimulating hormone, TSH)濃度，我們發現76.9%、12.3% 及10.8%之TGA/TMA陽性RAS患者，分別有正常、較低及較高之血清TSH濃度。另外AG+/RAS及AG-/RAS患者，皆有較低之平均血色素、血清鐵及維生素B12濃度，且其血色素、血清鐵、維生素B12及葉酸缺乏頻率，皆比健康控制組個體為高。另外AG+/RAS患者有較低之平均血色素及血清鐵(只有女性患者)濃度，且其血色素及血清鐵缺乏頻率，皆比AG-/RAS患者為高。69位貧血AG+/RAS患者中，30位 (43.5%)為正常血球性貧血、23 位(33.3%)為缺鐵性貧血、16位 (23.2%)為其他型態貧血。38位貧血AG-/RAS患者中，26位 (68.4%)為正常血球性貧血、5位 (13.2%)為缺鐵性貧血、7位 (18.4%)為其他型態貧血。

結論：約三分之一RAS患者其血清中有GPCA、TGA或 TMA自體抗體存在，因為部分GPCA陽性患者，會發展成惡性貧血、自體免疫萎縮性胃炎或胃癌。部分TGA/TMA陽性患者，會引起自體免疫甲狀腺疾病，最後造成甲狀腺功能異常，因此這些GPCA、TGA或 TMA自體抗體陽性患者，必須轉診至內科檢查及治療。另外部分AG+/RAS及AG-/RAS患者有貧血及補血素缺乏情形，且AG+/RAS患者比AG-/RAS患者，有較嚴重之貧血及補血素缺乏情形。RAS合併AG或RAS疾病本身是造成AG+/RAS及AG-/RAS患者貧血及補血素缺乏之重要因子。

關鍵字：復發性口腔潰瘍、萎縮性舌炎、胃壁細胞抗體、甲狀腺球蛋白抗體、甲狀腺微小體抗體、貧血、補血素缺乏、鐵、維生素B12、葉酸

關鍵字

復發性口腔潰瘍 ； 萎縮性舌炎 ； 胃壁細胞抗體 ； 甲狀腺球蛋白抗體 ； 甲狀腺微小體抗體 ； 貧血 ； 補血素缺乏 ； 鐵 ； 維生素B12 ； 葉酸

並列摘要

II. Abstract
Background/Purpose: Recurrent aphthous stomatitis (RAS) is a common oral mucosal disease characterized by recurrent and painful ulcerations on the nonkeratinized oral mucosa. Some of RAS patients have concomitant atrophic glossitis (AG). The purposes of this study were to examine the frequencies of presence of serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) in different types of RAS patients, to evaluate whether AG-positive RAS (AG+/RAS) patients or AG-negative RAS (AG-/RAS) patients had anemia and hematinic deficiencies, and to assess whether RAS combined with AG or RAS itself was a significant factor causing anemia and hematinic deficiencies in AG+/RAS or AG-/RAS patients, respectively.

Methods: The mean blood hemoglobin (Hb) and serm iron, vitamin B12, folic acid, GPCA, TGA, and TMA levels were measured in 355 RAS patients of different subtypes and in 355 age- and sex-matched healthy control subjects.

Results: We found that 13.0%, 19.4%, and 19.7% of 355 RAS patients, 16.7%, 23.3%, and 21.7% of 60 major-typed RAS patients, 12.2%, 18.6%, and 19.3% of 295 minor-typed RAS patients, 18.1%, 20.0%, and 21.9% of 160 AG+/RAS patients, and 8.7%, 19.0%, and 17.9% of 195 AG-/RAS patients had the presence of GPCA, TGA, and TMA in their sera, respectively. RAS, major-typed RAS, minor-typed RAS, AG+/RAS, and AG-/RAS patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). Of 65 TGA/TMA-positive RAS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 76.9%, 12.3%, and 10.8% of these TGA/TMA-positive RAS patients had normal, lower, and higher serum TSH levels, respectively. Moreover, both AG+/RAS and AG-/RAS patients had significantly lower mean Hb, iron, and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies than healthy control subjects. Furthermore, AG+/RAS patients had significantly lower mean Hb and serum iron level (for women only) and significantly greater frequencies of Hb and iron deficiencies than AG-/RAS patients. Of 69 anemic AG+/RAS patients, 30 (43.5%) had normocytic anemia, 23 (33.3%) had iron deficiency anemia, and 16 (23.2%) had other types of anemia. Of 38 anemic AG-/RAS patients, 26 (68.4%) had normocytic anemia, 5 (13.2%) had iron deficiency anemia, and 7 (18.4%) had other types of anemia.

Conclusions: We conclude that approximately one-third RAS patients may have GPCA/TGA/TMA positivity in their sera. Because part of GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these patients should be referred to medical doctors for further management. Moreover, some of AG+/RAS or AG-/RAS patients do have anemia and hematinic deficiencies and AG+/RAS patients do have severer anemia statuses and iron deficiency than AG-/RAS patients. RAS combined with AG or RAS itself does play a significant role in causing anemia and hematinic deficiencies in AG+/RAS or AG-/RAS patients, respectively.

Keywords: recurrent aphthous stomatitis; atrophic glossitis, gastric parietal cell antibody, thyroglobulin antibody, thyroid microsomal antibody, anemia, hematinic deficiency, iron, vitamin B12, folic acid

並列關鍵字

recurrent aphthous stomatitis ； atrophic glossitis ； gastric parietal cell antibody ； thyroglobulin antibody ； thyroid microsomal antibody ； anemia ； hematinic deficiency ； iron ； vitamin B12 ； folic acid

參考文獻

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